Describe mechanisms of how immunonutrition benefits patients in surgery beyond that of treating or preventing malnutrition

Transcription

1 Juan B. Ochoa MD, FACS Professor of Surgery and Critical Care University of Pittsburgh Medical and Scientific Director, Nestlé HealthCare Nutrition, NestléHealthScience North America Sponsor Disclosure: This presentation has been prepared and sponsored by Nestlé HealthCare Nutrition, Inc. The material herein is for educational purposes only and is not intended as a substitute for medical advice. Reproduction or distribution of these materials is prohibited. Copyright 2012 Nestlé. All rights reserved. 1 Objectives: 1) Describe mechanisms of how immunonutrition i i benefits patients in surgery beyond that of treating or preventing malnutrition 2) Identify the clinical evidence showing improved outcomes with perioperativeimmunonutritionimmunonutrition 3) List quality improvement processes aimed at incorporating immunonutrition in major elective surgery 2 1

2 What a Surgical Patient Wants Receive care that allows the best chances of having an uneventful and rapid recovery Absence of Complications such as infection Tolerable and manageable pain Minimal disruption to daily activities Courteous, respectful and friendly care + 3 Reducing Risk of Infection after Surgery PATHOGEN IMMUNONUTRITION ENVIRONMENT HOST 4 2

3 Post operative infections are an increasing burden to healthcare providers Infections are the most frequent cause of morbidity after surgery Up to 54% of all HAIs (Healthcare Associated Infections) occur in high risk surgical populations. Dept of Health and Human Services (HHS) has identified the following infections account for approximately 75% of HAIs in acute care hospitals: 34% urinary tract infections 17% surgical site infections 14% bloodstream infections 13% pneumonia Surgical site infections costing the system $ billion Klevens RM et al. Public Health Rep 2007, Richards MJ et al. Inf Cont Hosp Epid 2000 Scott RD. CDC The Patient s Journey through Surgery Pre Intra Post NUTRITION INTERVENTION Rehabilitation 7 3

4 Poll Question #1 Whichelectivesurgerypatient population has benefited from preoperative oral nutrition intervention? a. Malnourished patients only b. Malnourished and well nourished patients c. No surgical patient population has benefited from preoperative nutrition intervention 8 Nutrition Status Predicts Surgical Outcome Highly important predictor of outcome Affects all surgical illnesses Is independent of the volitional capacity of the patient Kudsk KA, Tolley EA, DeWitt RC et al. Preoperative albumin and surgical site identify surgical risk for major postoperative 9 complications. JPEN J Parenter Enteral Nutr 2003; 27:1-9. 4

5 What Does this Mean? Malnutrition Normal That surgical nutrition intervention should only be used for malnourished patients? NO! Surgery imposes unique nutrition requirements independent of the patient s underlying nutritional status tt Nutrition intervention aimed at meeting the unique nutritional requirements benefits ALL surgical patients 10 Major Surgery Imposes Unique Nutrition Requirements Mj Major surgery decreases arginine i availability Major Elective Surgery T cell Proliferation Collagen Production Arginine is important for immune function and healing Omega 3 fatty acids may modulate arginine metabolism 11 5

6 Surgery Patients are more Susceptible to Infection due to Arginine Deficiency T Cell Dysfunction Risk of INFECTION Arginine Deficiency Immunonutrition restores plasma arginine levels to support decreased risk of infections Popovich 2006; McClave 2009; Zhu Yes, Arginine Deficiency A set of signs and symptoms associated with the loss of a specific nutrient T lymphocyte dysfunction NO production Clinical consequences Increased infections, poor microcirculation, poor wound healing Mechanism Arginase Therapy Surgical Immunonutrition Protocol However, must include more than Arginine replacement to see benefit (Popovic, Zeh, Ochoa 2006) 15 6

7 Is Arginine the Whole Story? n 3 fatty acids EPA and DHA from Fish Oil Minimize inflammatory response by decreasing production of inflammatory mediators Increase immune response by enhancing lymphocyte function Interaction with Arginine metabolism? Calder P. Am J Clin Nutr Jun;83(6 Suppl):1505S 1519S. 16 Fish oil may Blunt Arginase 1 Expression PGE1 Borage Oil PGE2 Corn Oil PGE3 Fish Oil Arginase expression may be modified by the type of Fatty Acid Given to a Patient Bansal and Syres JPEN

8 Evidence Based Outcomes: Marik Meta Analysis Summary of Studies Included in Meta-Analysis Timing of Formula Number of Immunonutrition Author Year Setting Immunonutrients t Blind Patients t Pre-op (n=1) Xu 2006 GI malignancy A N 60 Daly 1992 GI malignancy A N 85 Daly 1995 GI malignancy A Y 60 Kenler 1996 GI malignancy B Y 35 Braga 1996 GI malignancy A Y 40 Schilling 1996 GI malignancy A N 28 Gianotti 1997 GI malignancy A N 174 Senkal 1997 GI malignancy A Y 154 Post-op (n=15) Braga 1998 GI malignancy A Y 110 Snyderman 1999 H&N malignancy A Y 129 Di Carlo 1999 GI malignancy A N 68 De Luis 2002 H&N malignancy C Y 47 Jiang 2004 GI surgery D Y 120 Farreras 2005 GI malignancy A Y 60 Lobo 2006 GI malignancy D Y 108 Formulas: A arg/n3/nucleotides B n3 alone C arg alone D arg n3 (n= 1918) Peri-op (n=5) Casas-Rodera 2008 H&N malignancy C Y 30 Braga 1999 GI malignancy A Y 206 Senkal 1999 GI malignancy A Y 154 Tepaske 2001 Cardiac surgery A Y 50 Braga 2002 GI malignancy A Y 100 Helminen 2007 GI surgery A Y 100 Marik PE, Zaloga GP. JPEN. 2010;34: Immunonutrition vs. Control Formulas High-Risk Patients Undergoing Elective Surgery who Received Immunonutrition Formulas Risk of Hospital Acquired Infections Significantly Reduced by 38% - 61% OR 0.49; 95% CI, , P< vs. control formula Wound Complications Significantly Reduced by 9% - 60% OR 0.60; 95% CI, , P=0.02 vs. control formula Hospital Length of Stay Reduced on Average by 3 Days days; 95% CI, to days, P< vs. control formula Benefits of immunonutrition required use of formulas containing both Arginine and Fish oil Pre op use starting at least 5 days prior to surgery and continuing post op when feasible advised Marik PE, Zaloga GP. JPEN. 2010;34:

9 Evidence Based Outcomes: Drover Meta Analysis 35 studies in major elective surgery (n= 3438) n= /35 studies in elective GI surgery Evaluated pre, peri and post operative use of arginine supplemented diets (immunonutrition) on outcomes: Primary outcome Infectious complications reduced by 41% (p< ) 00001) Secondary outcomes Hospital LOS reduced WMD 2.38 days (p< ) Mortality: No change Various sub analyses Drover et al. J Am College Surgeons Mar Sub analyses of Arginine Supplemented (Immunonutrition) Formulas on Infection Figure 4. Results of Subgroup Analyses examining the Effect of Arginine Supplemented Diets on Infection Same benefit shown for GI surgery vs non GI surgery Same benefit shown for Upper and Lower GI surgeries Only Arg n3 nucleotide formula showed statistically significant benefit when compared with ihother arginine i supplemented formulas (p<0.0001) Peri operative use showed greatest benefit (p= 0.03) Drover et al. J Am Coll Surgeons Mar 2011 GI studies (21) Non GI studies (7) Lower GI studies (1) Upper GI studies (16) Lower & Upper GI studies (4) Arg+FO+nucleo (21) Other (7) Pre Op studies (6) Peri Op studies (9) Post Op studies (15) Infections Overall P=0.28 P=0.06 P< P=0.03 P< Arginine Beneficial RR Arginine Harmful Number in parenthesis indicates number of studies 21 9

10 Sub analyses of Arginine supplemented diets on LOS Figure 5. Results of Subgroup Analyses examining the Effect of Arginine Supplemented Diets on Length of Stay GI studies (21) P= Significantly more benefit shown for: Non GI surgery (p=0.0007) Non GI studies (8) Lower GI studies (2) Upper GI studies (14) Lower & Upper GI studies (5) P=0.004 Upper GI Surgery (p=0.004) Use of a formula containing Arg n3 nucleotides (p<0.0001) Peri operative use (p=0.001) Arg+FO+nucleo (21) Other (8) Pre Op studies (6) Peri Op studies (11) Post Op studies (14) P< P=0.001 Number in parenthesis indicates number of studies Length of Stay Overall P< Drover et al. J Am Coll Surgeons Mar WMD Weighted Mean Difference (in days) 22 Evidence Based Outcomes: Waitzberg Meta Analysis 17 randomized trials in elective GI cancer, H/N cancer and cardiac surgical patients n= 2305 Compared the same immunonutrition formula with control nutrition intervention Examined relationship between pre, peri and postoperative immunonutrition and outcomes: Post op infectious complications reduced by 39% 61% (p<0.0001) Anastomotic leaks: by 44% (p=0.004) Pneumonia: by 47% (p<0.0001) Wound infections: by 40% (p=0.005) Abdominal abscesses: by 54% (p=0.001) UTI: by 47% (p=0.011) Waitzberg et al, WJS Hospital LOS: 2 days less on average (p<0.0001) 23 10

11 Waitzberg Meta Analysis Take Aways Immunonutrition supplementation appears warranted in major elective surgical patients as part of a proactive approach to infection control Clinical benefit shown for pre, post and peri operative use of an immunonutrition formula containing a blend of: L Arginine Omega 3 fatty acids (fish oil) Dietary nucleotides Where preoperative use not possible, early postoperative immunonutrition supplementation can improve outcomes beyond standard nutrition Waitzberg et al. WJS The Role of Nucleotides Building blocks for DNA and RNA Indispensable in stressed states Essential for rapidly replicating cells to help support immune function Required for almost all cell activities and growth Arginine helps stimulate synthesis in vitro Yamauchi K et al. Nutrition (2002) 25 11

12 Effect of Immunonutrition Intervention Colorectal Surgery Well nourished Patients (albumin g/dl) n=100 P<0.05 P<0.04 Preop Arg n3 nuc Standard NS Oral Immunonutrition Supplement Arginine Omega 3 Fatty Acids Nucleotides 2 0 Braga et. al. Infection Anast. Leak Surgery 2002;132: Immunonutrition increases Tissue Oxygenation Braga et al. Surgery 2002;132:

13 Immunonutrition increases T lymphocyte Function Braga et. al. Surgery 2002;132: Immunonutrition decreases Inflammation Braga et. al. Surgery 2002;132:

14 Critical Care Guidelines Immunonutrition E1: IMMUNE MODULATING ENTERAL FORMULATIONS CONTAINING INGREDIENTS SUCH AS: Arginine Glutamine Nucleic acid (Nucleotides) Omega 3 fatty acids Antioxidants SHOULD BE USED FOR APPROPRIATE PATIENT POPULATIONS: Major elective surgery, trauma, burns, head/neck cancer Critically ill patients on mechanical ventilation WITH CAUTION IN PATIENTS WITH SEVERE SEPSIS Surgical ICU (Grade A) Medical ICU (Grade B) SCCM/ASPEN, McClave S JPEN Cancer Surgery Guidelines Immunonutrition Cancer Care Nutrition Guidelines Guideline 10: IMMUNE ENHANCING ENTERAL FORMULATIONS CONTAINING MIXTURES OF: Arginine Nucleic acids (Nucleotides) n 3 Fatty Acids GRADE A May be beneficial in Malnourished Patients Undergoing Major Cancer Operations August DA, Huhmann MB, A.S.P.E.N. Clinical Guidelines JPEN

15 Surgery Guidelines: Immunonutrition Surgery Nutrition Guidelines Guideline 4.2.3: USE ENTERAL NUTRITION WITH IMMUNO MODULATING SUBSTRATES: Arginine, Nucleic acids (Nucleotides), and Omega 3 fatty acids GRADE A Peri operatively and independent of nutritional risk for those patients: Undergoing major neck surgery for cancer Undergoing major abdominal cancer surgery After severe trauma Weimann A et al ESPEN Guidelines Clin Nutr Conclusions Immunonutrition and Evidence Based Medicine Arginine, i omega 3 fatty acid, nucleotides Ample evidence of benefit (level 1, Grade A) Integral to every aspect of care of the surgical patient s journey Can and should be done Preop and Postop Sf Safe Reduces morbidity, cost and may reduce mortality in high risk groups 33 15

16 Surgical Immunonutrition Protocol A New Standard of Care 5 Days Preoperatively At least 5 Days Postoperatively if feasible 500 ml 1000 ml IMF formula/day At least 1000 kcal IMF formula/day (meet at least 50 65% of needs) Waitzburg 2006; Marik 2010; McClave 2009; August 2009; Drover 2011 IMF= Immunonutrition Formula containing Arginine n3 fatty acid nucleotides 34 How do we Implement? Quality Practice Improvement (QPI) in Surgery QPI is the discipline that focuses on creating the optimal conditions that allow the patient an uneventful and rapid recovery from surgery at the lowest health care cost possible 35 16

17 From Science to QPI Science Integration of Evidence Creation of Bundle Measuring Compliance Effects on Outcome 36 Keys to Implementing a QPI: Surgical Immunonutrition Protocol Surgeon stressing importance of nutrition the basics first, the peri operative protocol second Education with patient and caregiver on the basics and h i li i i l the surgical immunonutrition protocol Evans S. NNI Breakfast Seminar at ACS

18 Keys to Implementing a QPI: Show the Health Economics Is surgical immunonutrition cost effective? How about cost saving? saving? 41 Health Economics of Immunonutrition Previous studies Braga M et al. Nutrition 2005 Strickland A et al. JPEN 2005 Farber MS et al. JPEN 2005 Senkal M et al. CCM 1997 Shulkin DJ et al. Arch Surg

19 Studying cost/benefit of Surgical Immunonutrition Intervention Focus on the most studied population: GI Cancer Surgery Select outcomes associated with the most studied combination of immunonutrients to reduce variables Utilize a large, reputable US database to identify costs associated with infectious complications and LOS in GI cancer surgery 43 Peri operative Immunonutrition Health Economic Model Cost for GI Patients without Immunonutrition Part ti: Outcomes of Peri operative Immunonutritio n Part II: US Hospital Cost Data Cost for GI Patients with Immunonutrition Model that Estimates Potential Hospital Cost Savings for GI Cancer Surgery Mauskopf J et al. ESPEN 2011; Submitted for publication 44 19

20 Part II: US Hospital Cost Data Healthcare Cost and Utilization Project (HCUP) Largest all payer database in US 8 million hospital stays Representative of all US hospital stays Charges converted to costs using facility specific cost to charge ratios provided by HCUP 2008 costs adjusted to 2010 dollars HCUP Nationwide Inpatient Sample (NIS). Healthcare Cost and Utilization Project (HCUP) Agency for Healthcare Research and Quality, Rockville, MD. us.ahrq.gov/nisoverview.jsp 46 Part II: US Hospital Cost Data Healthcare Cost and Utilization Project (HCUP) Estimated average cost per hospital stay for GI cancer surgery Without infectious complications: $19,629 (n= 14,042 ) With infectious complications: $41,119 (n= 5,315 ) 20.8% with infectious complications in HCUP Waitzberg was 25% 31% HCUP Nationwide Inpatient Sample (NIS). Healthcare Cost and Utilization Project (HCUP) Agency for Healthcare Research and Quality, Rockville, MD. us.ahrq.gov/nisoverview.jsp 47 20

21 Peri operative Immunonutrition* Estimated Potential Savings Based on Reduction in Risk of Complications** Clinical Outcomes (Waitzberg et al 2006) Base complication rate 31.32% Reduction in risk of complications with immunonutrition 53% Calculated Costs Hospital cost/stay with complications $41,119 Hospital cost/stay with complications $19,629 *Containing arginine, n 3 fatty acids and nucleotides; Cost of immunonutrition not included. **Estimated potential cost savings included in this health economics model are for illustrative purposes only and are not intended to guarantee any specific reductions in cost at a particular facility. 48 Sensitivity Analysis Complications Method* Estimated Potential Cost Savings/Patient** Potential Sav vings ($) per patient sta ay $2371 $1710 $1140 $342 $ Base Complication Rate (%) USD *Containing arginine, n 3 fatty acids and nucleotides; Cost of immunonutrition not included. **Estimated potential cost savings included in this health economics model are for illustrative purposes only and are not intended to guarantee any specific reductions in cost at a particular facility

22 WHAT IF Surgical Immunonutrition was Standard of Care for GI Surgery in the US? CDC Cases 3.2 million cases GI surgery/year X $2,371 potential estimated savings/stay = $7.6 Bn HE models in cardiac and head/neck surgery have not yet been explored CDC Nat Health Statistics. 29; 2010 (data from 2007) HCUP Conclusions Surgical immunonutrition given peri operatively supports Decreased dinfections i Decreased complications Saving of healthcare costs Demonstrated in GI cancer surgery patients Surgical immunonutrition needs to be standard of care How can you help to improve care by implementing this QPI? 52 22

23 Poll Question #2 Which of the responses below best describes the largest barrier you currently face to putting a peri operative surgical immunonutrition protocol into practice? a. Lack of knowledge by medical staff about the benefits of immunonutrition b. Concerns with cost c. Lack of availability of product d. Already use immunonutrition before and after certain major elective surgeries 53 Thank You Sponsor Disclosure: This presentation has been prepared and sponsored by Nestlé HealthCare Nutrition, Inc. The material herein is for educational purposes only. Reproduction or distribution of these materials is prohibited. Copyright 2012 Nestlé. All rights reserved